Action Points

Note that this randomized trial found that intensive blood pressure control did not reduce the risk of ICH expansion among a subset of those with ICH who had a positive CT angio "spot sign."

However, the spot sign itself was a relatively poor marker for ICH expansion, in contrast to findings in prior smaller studies.

The predictive performance of the computed tomographic angiography (CTA) spot sign for intracerebral hemorrhage (ICH) expansion may not be as high as previously thought, according to results from a secondary analysis of a randomized clinical trial.

The study also failed to show evidence that intensive blood pressure (BP) reduction lowered the risk for hematoma expansion or improved functional outcomes in spot sign-positive participants with ICH, Andrea Morotti, MD, of Massachusetts General Hospital in Boston, and colleagues reported online in JAMA Neurology.

The CTA spot sign had a sensitivity of 0.54 and specificity of 0.63 for hematoma growth greater than 33%, the SCORE-IT (Spot Sign Score in Restricting ICH Growth) study showed. The highest positive predictive values (PPV) seen in this prospective observational study -- nested in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) trial -- were seen in the first two hours (0.61).

In addition, the proportion of patients with a spot sign and a 90-day modified Rankin Scale score of 4 or greater (range 0-6) was 20 of 27 in those who underwent intensive BP reduction (systolic BP target <140 mm Hg) within 4.5 hours from onset. By comparison, 10 of 20 patients who underwent standard BP reduction therapy (systolic BP target <180 mm Hg) had the same unfavorable outcome.

"We report 2 major findings in this study," the study authors stated. "For the first time, to our knowledge, we have prospectively validated that a CTA spot sign is associated with hematoma expansion, but the diagnostic accuracy of this marker was lower compared with findings in previous single-center studies. Second, even in patients with a CTA spot sign (and thus a higher risk for expansion), we found no evidence that intensive BP reduction lowers the risk for expansion or improves outcome."

Previous studies have shown that in the acute setting, the CTA spot sign indicated active bleeding and early hematoma expansion, the study authors pointed out. Others have demonstrated a strong correlation between the initial ICH volume and worse clinical outcomes, particularly when there is a positive spot sign on CTA.

The study, which was carried out at 59 sites from May 2011 through December 2015, included 133 consecutive ATACH-II participants with primary ICH who underwent CTA within 8 hours of symptom onset. Data analysis for SCORE-IT was completed between July 1 through Aug. 31, 2016.

Mean age of the 83 men and 50 women who participated was 62 years. In this group, 53 (39.8%) had a spot sign, and 24 of 123 (19.5%) experienced ICH expansion.

In an accompanying editorial, Jimmy Berthaud, MD, MPH, and Bradford Worrall, MD, MSc, of the University of Virginia Health System in Charlottesville, said that the SCORE-IT findings, taken in context with previous studies, indicate that the spot sign story is likely more complex than previously thought. They also credited the researchers with highlighting "the important point that the spot sign independently cannot precisely predict those participants who will have early hematoma expansion."

Although the positive predictive value (PPV) of the CTA spot sign for hematoma expansion varies widely across studies, the diagnostic accuracy of the spot-sign marker in SCORE-IT was lower than in prior single-center study reports, the editorialists noted. "As applied in the present study, the spot sign cannot select those for whom intensive blood pressure reduction might lower the risk for hematoma expansion or improve functional outcome."

Results from an earlier study "emphasized the importance of earlier imaging for selecting participants with ICH who might best benefit from intensive blood pressure reduction," they pointed out, adding that the PPV of the CTA spot sign "might have been higher if participants were selected at a shorter time window than the 8-hour cutoff used in this study." The ATACH-II was stopped early after showing no difference in death or disability between treatment arms.

Differences in sensitivity and specificity between the study's two common spot sign definitions also "have important implications," the editorialists emphasized. For instance, the lack of sensitivity and specificity for predicting ICH definition with definition 1 -- taken from the Massachusetts General Hospital -- makes it difficult to apply clinically. On the other hand, the higher specificity seen with definition 2 -- taken from the Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign (PREDICT) study -- makes it possible to select for patients at higher risk of ICH.

In SCORE-IT, 20% of participants experienced hematoma expansion, and 56 of 123 participants (45.5%) had a poor functional outcome at 90 days. The observed case-fatality rate of 8.3% with ICH was different from the rate of 30% to 40% seen in a "real-world population," Berthaud and Worrall said.

An increase in study power with an older study population with ICH might have demonstrated an association between blood pressure control and outcomes, the editorialists suggested. A 2001 study describing a simple, reliable grading scale for ICH demonstrated a strong association between an age of 80 years or older and 30-day mortality (OR 9.84, P=0.001), they said.

This study was funded by the National Institute of Neurological and Communicative Disorders and Stroke. Morotti reported no conflicts of interest. Co-author Joshua N. Goldstein, MD, PhD, disclosed relationships with Boehringer Ingelheim, Pfizer, Portola and Bristol Myers Squibb. No other disclosures were reported. Editorialist Worrall reported serving as the deputy editor of Neurology. Co-author Berthaud disclosed no conflicts of interest.

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